regulating total water volume and total solute concentration in water

© 2013 Pearson Education, Inc.

Kidney Functions

• Regulating total water volume and total solute concentration in water

• Regulating ECF ion concentrations• Ensuring long-term acid-base balance• Removal of metabolic wastes, toxins,

drugs


Kidney Functions

• Endocrine functions– Renin - regulation of blood pressure– Erythropoietin - regulation of RBC

production• Activation of vitamin D


Urinary System Organs

• Kidneys - major excretory organs• Ureters - transport urine from kidneys to

urinary bladder• Urinary bladder - temporary storage

reservoir for urine• Urethra transports urine out of body


Figure 25.1 The urinary system.

Hepatic veins (cut)

Esophagus (cut)Inferior vena cava

Adrenal gland

Aorta

Iliac crest

Rectum (cut)Uterus (part of femalereproductive system)

Renal arteryRenal hilumRenal vein

Kidney

Ureter

Urinarybladder

Urethra


Internal Anatomy

• Renal cortex– Granular-appearing superficial region

• Renal medulla– Composed of cone-shaped medullary (renal)

pyramids


Figure 25.4a Blood vessels of the kidney. Cortical radiatevein Cortical radiatearteryArcuate vein

Interlobar veinInterlobar arterySegmental arteriesRenal vein

Renal arteryRenal pelvis

Ureter

Renal medulla

Renal cortex

Arcuate artery

Frontal section illustrating major blood vessels


Nephrons

• Structural and functional units that form urine

• > 1 million per kidney• Two main parts

– Renal corpuscle– Renal tubule


Renal Corpuscle

• Two parts of renal corpuscle– Glomerulus

• Tuft of capillaries; fenestrated endothelium highly porous allows filtrate formation

– Glomerular capsule (Bowman's capsule)• Cup-shaped, hollow structure surrounding

glomerulus


Figure 25.5 Location and structure of nephrons.Renal cortexRenal medulla

Renal pelvis

UreterKidney

Renal corpuscle• Glomerular capsule• Glomerulus

Proximal convolutedtubule

Cortex

Medulla

ThicksegmentThin segment

Nephron loop• Descending limb• Ascending limb

Collectingduct

Glomerular capsule: parietal layerBasementmembrane

Podocyte Fenestrated endotheliumof the glomerulus

Glomerular capsule: visceral layerApical

microvilliMitochondria

Highly infolded basolateralmembrane

Proximal convoluted tubule cellsApical side

Basolateral sideDistal convoluted tubule cells

Nephron loop (thin-segment) cells

Principalcell

Intercalated cell

Collecting duct cells

Distal convolutedtubule


Renal Tubule

• Three parts– Proximal convoluted tubule

• Proximal closest to renal corpuscle– Nephron loop– Distal convoluted tubule

• Distal farthest from renal corpuscle -> Collecting duct


Renal Tubule

• Proximal convoluted tubule (PCT) – Cuboidal cells with dense microvilli (brush

border surface area); large mitochondria– Functions in reabsorption and secretion– Confined to cortex


Renal Tubule

• Nephron loop– Descending and ascending limbs – Distal descending limb = descending thin

limb; simple squamous epithelium– Thick ascending limb

• Cuboidal to columnar cells; thin in some nephrons


Renal Tubule

• Distal convoluted tubule (DCT)– Cuboidal cells with very few microvilli – Function more in secretion than reabsorption– Confined to cortex


Collecting Ducts

• Receive filtrate from many nephrons• Two cell types

– Principal cells• Sparse, short microvilli• Maintain water and Na+ balance

– Intercalated cells• Cuboidal cells; abundant microvilli; two types

– A and B; both help maintain acid-base balance of blood


Classes of Nephrons

• Cortical nephrons—85% of nephrons; almost entirely in cortex

• Juxtamedullary nephrons– Long nephron loops deeply invade medulla Important in production of concentrated urine


Figure 25.7a Blood vessels of cortical and juxtamedullary nephrons.Cortical nephron

• Short nephron loop• Glomerulus further from the cortex-medulla junction• Efferent arteriole supplies peritubular capillaries

Juxtamedullary nephron• Long nephron loop• Glomerulus closer to the cortex-medulla junction• Efferent arteriole supplies vasa recta

Renalcorpuscle

Glomerulus(capillaries)Glomerularcapsule

Proximalconvolutedtubule

PeritubularcapillariesAscendinglimb ofnephron loop

KidneyArcuate veinArcuate arteryNephron loop

Efferentarteriole

Descendinglimb ofnephron loop

Cortical radiate vein

Afferent arterioleDistal convoluted tubule

Efferentarteriole

Vasa recta

Cortex-medullajunction

Cortical radiate artery

Collecting duct

Afferent arteriole


Nephron Capillary Beds

• Renal tubule associated with two capillary beds– Glomerulus– Peritubular capillaries

• Juxtamedullary nephron associated withVasa recta– Important in regulation of rate of filtrate

formation and blood pressure



• Glomerulus - specialized for filtration• Different from other capillary beds – fed

and drained by arteriole– Afferent arteriole glomerulus efferent

arteriole• Blood pressure in glomerulus high

because– Afferent arterioles larger in diameter than

efferent arterioles– Arterioles are high-resistance vessels



• Peritubular capillaries– Low-pressure, porous capillaries adapted for

absorption of water and solutes – Arise from efferent arterioles– Cling to adjacent renal tubules in cortex– Empty into venules


Juxtaglomerular Complex (JGC)

• Two important cell type:– Macula densa, granular cells, – Macula densa:– Tall, closely packed cells of ascending limb– Chemoreceptors; sense NaCl content of filtrate

• Granular cells (juxtaglomerular, or JG cells)– Enlarged, smooth muscle cells of arteriole– Secretory granules contain enzyme renin– Mechanoreceptors; sense blood pressure in afferent

arteriole


Juxtaglomerular Complex (JGC)

• Granular cells (juxtaglomerular, or JG cells)– Enlarged, smooth muscle cells of arteriole– Secretory granules contain enzyme renin– Mechanoreceptors; sense blood pressure in

afferent arteriole


Figure 25.8 Juxtaglomerular complex (JGC) of a nephron.

GlomerularcapsuleEfferent arteriole

Afferent arteriole

Glomerulus

Efferentarteriole

JuxtaglomerularcomplexMacula densacellsof the ascendinglimb of nephron loop

• Extraglomerular• Granular cells Afferent

arteriole

Parietal layerof glomerularcapsule

Capsularspace

Footprocessesof podocytes

Podocyte cell body (visceral layer)

Red blood cellProximaltubule cell

Lumens of glomerularcapillaries

Endothelial cellof glomerularcapillary

Glomerular mesangialcells

Renal corpuscleJuxtaglomerular complex

mesangial cells

•


Kidney Physiology: Mechanisms of Urine Formation• Three processes in urine formation and

adjustment of blood composition– Glomerular filtration– Tubular reabsorption– Tubular secretion


Kidney Physiology: Mechanisms of Urine Formation• Glomerular filtration – produces cell- and

protein-free filtrate• Tubular reabsorption

– Selectively returns 99% of substances from filtrate to blood in renal tubules and collecting ducts

• Tubular secretion– Selectively moves substances from blood to

filtrate in renal tubules and collecting ducts


Kidney Physiology: Mechanisms of Urine Formation• Filtrate (produced by glomerular filtration)

– Blood plasma minus proteins• Urine

– <1% of original filtrate– Contains metabolic wastes and unneeded

substances


Figure 25.9 A schematic, uncoiled nephron showing the three major renal processes that adjust plasma composition.

Corticalradiateartery

Afferentarteriole Glomerular

capillaries

Efferent arteriole

Glomerular capsule

Renal tubule and collecting ductcontaining filtrate

Peritubularcapillary

To cortical radiate vein

Three majorrenal processes: Urine

Glomerular filtrationTubular reabsorptionTubular secretion

1

2

3

123


Glomerular Filtration

• Passive process• No metabolic energy required• Hydrostatic pressure forces fluids and

solutes through filtration membrane• No reabsorption into capillaries of

glomerulus


The Filtration Membrane

• Porous membrane between blood and interior of glomerular capsule– Water, solutes smaller than plasma proteins

pass; normally no cells pass • Three layers

– Fenestrated endothelium of glomerular capillaries

– Basement membrane (fused basal laminae of two other layers)

– Foot processes of podocytes with filtration slits; slit diaphragms repel macromolecules


Figure 25.10a The filtration membrane.

Efferentarteriole

Afferentarteriole

Glomerularcapillary covered bypodocytes that formthe visceral layer ofglomerular capsule

Parietal layerof glomerular capsule

Proximal convolutedtubule

Glomerularcapsular space Cytoplasmic extensions

of podocytes

Filtration slits

Podocytecell body

Fenestrations(pores)

Glomerular capillary endothelium (podocyte covering and basement membrane removed)

Footprocessesof podocyte

Glomerular capillaries and thevisceral layer of the glomerularcapsule


Figure 25.10c The filtration membrane.

Capillary

Fenestration(pore)

Filtration membrane• Capillary endothelium• Basement membrane• Foot processes of podocyte of glomerular capsule

Filtrationslit

Slitdiaphragm

Three layers of the filtration membrane

Foot processesof podocyte

Filtratein capsularspace

Plasma


The Filtration Membrane

• Macromolecules "stuck" in filtration membrane• Allows molecules smaller than 3 nm to pass

– Water, glucose, amino acids, nitrogenous wastes• Plasma proteins remain in blood maintains

colloid osmotic pressure prevents loss of all water to capsular space– Proteins in filtrate indicate membrane problem


Pressures That Affect Filtration

• Outward pressures promote filtrate formation– Hydrostatic pressure in glomerular

capillaries = Glomerular blood pressure• Chief force pushing water, solutes out of blood• Quite high – 55 mm Hg (most capillary beds ~ 26

mm Hg)– Because efferent arteriole is high resistance vessel with

diameter smaller than afferent arteriole


Pressures That Affect Filtration

• Inward forces inhibiting filtrate formation– Hydrostatic pressure in capsular space (HPcs)

• Pressure of filtrate in capsule – 15 mm Hg

– Colloid osmotic pressure in capillaries (OPgc)• "Pull" of proteins in blood – 30 mm Hg

• Sum of forces Net filtration pressure (NFP)– 55 mm Hg forcing out; 45 mm Hg opposing =

net outward force of 10 mm Hg


Net Filtration Pressure (NFP)

• Pressure responsible for filtrate formation (10 mm Hg)

• Main controllable factor determining glomerular filtration rate (GFR)


Figure 25.11 Forces determining net filtration pressure (NFP).

Efferentarteriole

Glomerularcapsule

Afferentarteriole

NFP = Net filtration pressure = outward pressures – inward pressures = (HPgc) – (HPcs + OPgc) = (55) – (15 + 30) = 10 mm Hg

HPgc = 55 mm Hg

OPgc = 30 mm Hg

HPcs = 15 mm Hg


Regulation of Glomerular Filtration

• Volume of filtrate formed per minute by both kidneys (normal = 120–125 ml/min)

• Constant GFR allows kidneys to make filtrate and maintain extracellular homeostasis– Goal of intrinsic controls - maintain GFR in kidney

• GFR affects systemic blood pressure GFR urine output blood pressure, and vice

versa– Goal of extrinsic controls - maintain systemic blood

pressure


Regulation of Glomerular Filtration

• Intrinsic controls (renal autoregulation)– Act locally within kidney to maintain GFR

• Extrinsic controls– Nervous and endocrine mechanisms that

maintain blood pressure; can negatively affect kidney function


Intrinsic Controls

• Two types of renal autoregulation– Myogenic mechanism– Tubuloglomerular feedback mechanism


Intrinsic Controls: Myogenic Mechanism

• Smooth muscle contracts when stretched BP muscle stretch constriction of

afferent arterioles restricts blood flow into glomerulus– Protects glomeruli from damaging high BP

BP dilation of afferent arterioles• Both help maintain normal GFR despite

normal fluctuations in blood pressure


Intrinsic Controls: Tubuloglomerular Feedback Mechanism• Flow-dependent mechanism directed by

macula densa cells; respond to filtrate NaCl concentration

• If GFR filtrate flow rate reabsorption time high filtrate NaCl levels constriction of afferent arteriole NFP & GFR more time for NaCl reabsorption

• Opposite for GFR


Extrinsic Controls: Renin-Angiotensin Mechanism• Triggered when the granular cells of the

JGA release reninangiotensinogen (a plasma globulin)

resin angiotensin Iangiotensin converting

enzyme (ACE) angiotensin II


Effects of Angiotensin II

1. Constricts arteriolar smooth muscle, causing MAP to rise

2. Stimulates the reabsorption of Na+

– Acts directly on the renal tubules– Triggers adrenal cortex to release

aldosterone

3. Stimulates the hypothalamus to release ADH and activates the thirst center


Effects of Angiotensin II

4. Constricts efferent arterioles, decreasing peritubular capillary hydrostatic pressure and increasing fluid reabsorption

5. Causes glomerular mesangial cells to contract, decreasing the surface area available for filtration


Extrinsic Controls: Renin-Angiotensin Mechanism• Triggers for renin release by granular cells

– Reduced stretch of granular cells (MAP below 80 mm Hg)

– Stimulation of the granular cells by activated macula densa cells

– Direct stimulation of granular cells via 1-adrenergic receptors by renal nerves

© 2013 Pearson Education, Inc.Figure 25.12

Stretch of smoothmuscle in walls of afferent arterioles

Blood pressure inafferent arterioles; GFR

Vasodilation ofafferent arterioles

GFR

Myogenic mechanismof autoregulation

Release of vasoactive chemical inhibited

Intrinsic mechanisms directly regulate GFR despitemoderate changes in blood pressure (between 80 and 180 mm Hg mean arterial pressure).

Extrinsic mechanisms indirectly regulate GFRby maintaining systemic blood pressure, whichdrives filtration in the kidneys.

Tubuloglomerularmechanism ofautoregulation

Hormonal (renin-angiotensin)mechanism Neural controls

SYSTEMIC BLOOD PRESSURE

GFR

Macula densa cellsof JG apparatus

of kidney

Filtrate flow andNaCl in ascending

limb of Henle’s loop

Targets

Granular cells ofjuxtaglomerular

apparatus of kidney

Angiotensinogen Angiotensin II

Adrenal cortex Systemic arterioles

(+) Renin

Release

Catalyzes cascaderesulting in conversion

(+)

(+)

(+)

Kidney tubules

Aldosterone

Releases

Targets

Vasoconstriction;peripheral resistance

Blood volume

Na+ reabsorption;water follows

Systemicblood pressure

(+)

(+) (–)

IncreaseDecrease

StimulatesInhibits

Baroreceptors inblood vessels of

systemic circulation

Sympatheticnervous system

(+)

(–)

Vasodilation ofafferent arterioles


Extrinsic Controls: Sympathetic Nervous System• Under normal conditions at rest

– Renal blood vessels dilated– Renal autoregulation mechanisms prevail


Extrinsic Controls: Sympathetic Nervous System• If extracellular fluid volume extremely low

(blood pressure low)– Norepinephrine released by sympathetic

nervous system; epinephrine released by adrenal medulla

• Systemic vasoconstriction increased blood pressure

• Constriction of afferent arterioles GFR increased blood volume and pressure

regulating total water volume and total solute concentration in water

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